Expert Point of View: George Demetri, MD

Invited discussant of the abstract, George Demetri, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, noted that metastatic soft-tissue sarcomas present with variable clinical behaviors but are nearly always incurable with any approach. “Therefore, our intent is to palliate and to prolong life with the highest possible quality,” he said.

He said the question that has “dogged the field” for more than 35 years is, “What is the best first-line treatment for metastatic disease?” Other questions include: Can all soft-tissue sarcomas be “lumped together,” ie, which types have reasonably similar behaviors when metastatic? And does combination chemotherapy meaningfully improve clinical outcomes, compared with single-agent chemotherapy?

The overall survival results were disappointing, although progression-free survival was prolonged by 3-plus months with the combination, he pointed out. Since the typical patient with metastatic soft-tissue sarcoma lives 13 months, “the results mean that sarcoma is controlled for approximately 20% longer with combination chemotherapy,” and this is meaningful to the patient, Dr. Demetri offered.

Targeting Specific Patients

There is a need to be able to target patients who derive benefit from tumor response and control despite the regimen’s toxicities, he said. “And we do need to take quality of life into account as we think of how to use these data,” he added.

Dr. Dimitri suggested that “the clinical question” should be changed, from “What is the best first-line therapy?” to “What is the best first-line therapy for a specific patient.” EORTC 62012 offers “solid data” upon which clinicians can make informed choices about this, he said.

Based on the findings, he would prescribe single-agent doxorubicin for asymptomatic patients. For patients who are symptomatic or if tumor shrinkage is required, he believes combination doxorubicin plus ifosfamide is often the preferred choice. ■

Disclosure:Dr. Demetri has been a consultant for Novartis, Pfizer, Sanofi-Aventis, GlaxoSmithKline, Johnson & Johnson, Merrimack Pharma, Foundation Medicine, Merck, ZioPharm, N-of-One, and Champions Biotechnology. He has received research support from Novartis, Pfizer, Sanofi-Aventis, GlaxoSmithKline, Johnson & Johnson, Merck, and Amgen. He is a member of the scientific advisory board for ZioPharm, N-of-One, Koltan Pharmaceuticals, and Blueprint Medicines.

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The addition of aggressively dosed ifosfamide to doxorubicin in the treatment of advanced soft-tissue sarcomas significantly delayed disease progression but did not improve survival in the randomized phase III EORTC 62012 trial conducted by the Soft Tissue and Bone Sarcoma Group of the European...